2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)-malononitrile ([F-18]FDDNP) PET imaging has been used for classifying and staging progressive diseases, including Alzheimer's disease (AD) and Chronic Traumatic Encephalopathy (CTE). More than a decade of clinical research experience in the U.S., Europe, and Asia has demonstrated the ability of [F-18]FDDNP to differentiate Alzheimer's disease (AD) from normal aging, mild cognitive impairment (MCI), and several other neurodegenerative diseases (e.g., progressive supranuclear palsy, dementia with Lewy bodies, and Down syndrome). The ability of [F-18]FDDNP to differentiate AD from normal aging is comparable to that of 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]FDG).
Moreover recent clinical research demonstrates a distinct [F-18]FDDNP binding pattern in retired athletes and military personnel with a history of traumatic brain injury and suspected CTE; and this pattern can be readily differentiated from that of AD. Currently there is no available biomarker that can detect suspected CTE in living people at risk, and other PET ligands for this purpose are very early in their development.
The clinical symptoms of suspected CTE and AD overlap making accurate diagnosis challenging particularly in older individuals when the risk of AD increases. Both suspected CTE and AD patients experience cognitive decline and dementia as well as behavioral and mood symptoms. Having an accurate tool that assists in the differentiation of these common late life conditions would be important. Moreover, in younger adults, identifying patients with suspected CTE from normal individuals would be important for assisting with enrollment in clinical trials of drug discovery or treatment.
The diagnosis of CTE is currently only confirmed at autopsy, and there is a tremendous need for a biomarker that can identify suspected CTE in living individuals. Such a biomarker would guide current treatment decisions: differentiating AD from suspected CTE would identify those patients with AD who would be most likely to respond to medications currently available for that condition. Although no effective treatments are yet available, preventive measures can be implemented if suspected CTE is identified, and, moreover, these individuals could be enrolled in appropriate clinical trials.
While [F-18]FDDNP PET imaging has been used for classifying and staging progressive diseases such as AD and CTE, accurate reading and interpretation of these images require experts who are nuclear medicine physicians or neurologists experienced in brain PET imaging to perform the task. Without established reading procedures, the interpretation of [F-18]FDDNP PET imaging results can be subjective.
Progressive neurological diseases involve gradual changes in disease-specific brain structures. If the number of brain structures involved is small (e.g., one or two structures), the changes tagged by a PET tracer (like [F-18]FDDNP or [F-18]FDG) and imaged with PET can be viewed by experts to determine the type of disease and the progressive stage, especially for large and monotonous changes. However, when there are multiple structural regions involved and the changes are subtle, it is frequently difficult for most practitioners to read the images to differentiate AD and CTE.